Spatial-Domain Low-Coherence Quantitative Phase Microscopy to Improve the Cytological Diagnosis of Pancreatic Cancer

Abstract

Use of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytology to detect pancreatic cancer is limited, with a high false negative rate mainly due to the relatively fewer number of completely cancerous cells. To improve the accuracy of EUS-FNA cytological diagnosis, we evaluated a novel optical system—spatial-domain low-coherence quantitative phase microscopy (SL-QPM)—to analyze nanoscale nuclear architecture on original cytology samples, especially those diagnosed as indeterminate for malignancy, with the goal of maintaining high specificity and reducing false positive rate. We performed SL-QPM on original cytology samples obtained by EUS-FNA from 40 patients with suspicious pancreatic solid lesions (27 adenocarcinomas, 5 neuroendocrine tumor, 8 chronic pancreatitis), including 13 cases that were cytologically indeterminate. Each diagnosis had been confirmed by follow-up surgical pathology. The SL-QPM-derived nanoscale nuclear architectural parameters distinguished pancreatic cancer from cytologically indeterminate cells. A logistic regression model using nuclear entropy and SD increased the sensitivity of cytology in identifying pancreatic cancer from 72% to 94% while maintaining 100% specificity. The SL-QPM-derived nanoscale nuclear architecture properties show great promise in improving the cytological diagnosis of EUS-FNA for pancreatic cancer and could be used when traditional cytopathology does not get an accurate diagnosis, and can be easily translated into a traditional clinical device.

Early screening and diagnosis strategies of pancreatic cancer: a comprehensive review

“…85%) for PDAC diagnosis than cytopathology alone. Furthermore, novel optical system‐spatial‐domain low‐coherence quantitative phase microscopy (SL‐QPM) was demonstrated to improve the accuracy of EUS‐FNA cytological diagnosis and increase the sensitivity of cytology for identifying pancreatic cancer from 72% to 94%, even when traditional cytopathology failed to allow an accurate diagnosis [ 62 ]. For differentiating between inflammatory masses and malignancies, it was found that endoscopic ultrasound‐guided fine‐needle biopsy (EUS‐FNB) possessed higher diagnostic accuracy and sensitivity than EUS‐FNA (93.0% and 86.6% vs .…”

“…In addition, Bournet et al [61] reported that pathological assessment combined with KRAS-mutation analysis using allelic discrimination showed higher accuracy (88% vs. 73%) and sensitivity (93% vs. 85%) for PDAC diagnosis than cytopathology alone. Furthermore, novel optical system-spatial-domain low-coherence quantitative phase microscopy (SL-QPM) was demonstrated to improve the accuracy of EUS-FNA cytological diagnosis and increase the sensitivity of cytology for identifying pancreatic cancer from 72% to 94%, even when traditional cytopathology failed to allow an accurate diagnosis [62]. For differentiating between inflammatory masses and malignancies, it was found that endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) possessed higher diagnostic accuracy and sensitivity than EUS-FNA (93.0% and 86.6% vs. 83.6% and 69.5%), and it should be considered as the preferred technique for diagnosing cancer in the setting of chronic pancreatitis [63].…”

Overview of MicroRNAs as Diagnostic and Prognostic Biomarkers for High-Incidence Cancers in 2021

“…The commonly used methods for the diagnosis and prognosis of cancers are (1) imaging examination: including X-ray, CT, magnetic resonance imaging (MRI), ultrasound, endoscopy, glucose metabolism technology and positron emission tomography (PET), radionuclide imaging examination and other imaging methods [ 3 , 4 , 5 ]; (2) molecular marker examination: including detection of tumor markers such as carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and various carbohydrate antigens (such as CA125 and CA19) and some tumor-related biochemical indicators such as acid phosphatase (ACP), estrogen receptor (ER), and progesterone receptor (PR) in serum urine of patients [ 4 , 6 , 7 , 8 , 9 ]; (3) pathological examination where the abnormal tissue samples are collected for pathological examination by techniques such as immunohistochemistry (IHC), HE staining, and fluorescence in situ hybridization (FISH) [ 10 , 11 ]; (4) detection of circulating tumor cells (CTC), such as detection of tumor cells in peripheral blood, which can be used to monitor and predict the prognosis of tumor metastasis [ 12 , 13 ]; (5) body fluid cytological diagnosis, including detection of tumor cells by sputum, urine and other liquids or by means of puncture [ 14 , 15 ]; and (6) other examinations: including digital rectal examination (DRE), fecal occult blood test (FOBT), and other diagnostic methods [ 16 , 17 ].…”